Etonitazene 6-nitro isomer → HCID 178466234, compound

Participants

Reaction Steps

{2-[2-(4-Ethoxy-benzyl)-6-nitro-benzoimidazol-1-yl]-ethyl}-diethyl-amine 43 (90 mg, 0.227 mmol) was dissolved in anhydrous ethanol (7 mL) in a dry argon purged flask. Palladium, 10 wt % on activated carbon (24 mg, 0.0227 mmol) is quickly added and the atmosphere from the flask evacuated by vacuum pump and replaced with hydrogen from a balloon. The atmosphere is evacuated from the flask and replaced with hydrogen twice more and the mixture stirred under a hydrogen atmosphere at room temperature. After 3 hours, thin layer chromatography in a solvent system of (5% 2M NH3 in methanol/95% dichloromethane) shows complete conversion to 44 3-(2-Diethylamino-ethyl)-2-(4-ethoxy-benzyl)-3H-benzoimidazol-5-ylamine, which is utilized without isolation. The mixture is filtered through a pad of celite to remove insolubles, the pad washed with anhydrous ethanol (7 mL) and the ethanolic solution of the amine 44 is charged to a small, argon purged flask fitted with a magnetic stirbar. Thiophene-2-carboximidothioic acid methyl ester hydroiodide 9a (129.5 mg, 0.454 mmol) is added to the flask and the reaction was stirred under Ar at ambient temperature for 44 hours. The solvent was evaporated and residue partitioned between H2O and ethyl acetate and 1M sodium hydroxide solution added to adjust pH to 8. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine (twice), dried over magnesium sulphate, filtered and concentrated to afford crude. The product was purified using silica gel column chromatography eluting with 3% methanol/97% dichloromethane to 5% methanol/95% dichloromethane to afford a yellow solid 45 N-[3-(2-Diethylamino-ethyl)-2-(4-ethoxy-benzyl)-3H-benzoimidazol-5-yl]-thiophene-2-carboxamidine. Yield: 38 mg (35.2%). 1H NMR (DMSO) δ: 0.81 (t, 6H, J=7.0), 1.28 (t, 3H, J=7.0), 2.35-2.50 (2×m, 6H), 3.97 (q, 2H, J=7.0), 4.07 (t, 2H, J=6.7), 4.21 (s, 2H), 6.42 (br s, 2H), 6.67-6.70 (m, 1H), 6.85-6.88 (m, 1H), 6.88 (d, 2H, J=8.6), 7.08-7.11 (m, 1H), 7.17 (d, 2H, J=8.7), 7.46 (d, 1H, J=8.5), 7.60 (d, 1H, J=5.2), 7.73 (d, 1H, J=3.6); MS (ESI): 476 (MH+, 100%).

Provenance & Evidence